Ligation of integrin α3β1 by laminin 5 at the wound edge activates Rho-dependent adhesion of leading keratinocytes on collagen
Ligation of integrin α3β1 by laminin 5 at the wound edge activates Rho-dependent adhesion of leading keratinocytes on collagen
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DOI：
10.1074/jbc.m103404200
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发表时间：
2001-11-23
影响因子：
4.8
通讯作者：
Carter, WG
中科院分区：
文献类型：
--
作者：
Nguyen, BP;Ren, XD;Carter, WG
表皮的损伤标志着角质形成细胞从内源性基底膜层粘连蛋白5的静止锚定向暴露的真皮胶原的迁移转变。在这项研究中，我们试图表征激活信号，将静止的角质形成细胞转化为迁移的前导细胞在伤口边缘。先前，我们报道了培养的人包皮角化细胞（HFKs）通过整合素α (2) β(1)在胶原蛋白上的粘附和扩散需要RhoGTP，一种肌动蛋白应激纤维的调节因子。相反，在层粘连蛋白5上的粘附和扩散需要整合素α (3) β(1)和α (6) β(4)，并依赖于磷酸肌苷3-羟基激酶（Nguyen, b.p., Gil, s.g., and Carter, w.g. (2000) J. Biol）。275年化学,31896 - 31907)。在这里，我们报道了静止的HFKs不粘附在胶原蛋白上，而是粘附并扩散在层粘连蛋白5上。通过使用胶原黏附作为转化为“领先伤口细胞”的一个标准，我们发现胶原黏附的激活需要RhoGTP的升高。静止的HFKs通过整合素α (3) β(1)和α (6) β(4)与层粘连蛋白5的粘附足以增加在胶原上粘附和扩散所需的RhoGTP水平。与此一致的是，静止的HFKs与层粘连蛋白5的粘附，而不是与胶原的粘附，也促进层粘连蛋白5前体的表达，这是表皮生长过程中主要角质形成细胞的一个特征。我们认为，静止表皮的损伤通过α (3) β(1)和α (6) β(4)以rho不依赖的机制在内源性基底膜层粘连蛋白5上启动伤口边缘角化细胞的粘附和扩散。通过α (3) β(1)在内源性层粘连蛋白5上扩散是必要的，但不足以提高前体层粘连蛋白5和RhoGTP的表达，从而允许随后的胶原通过α (2) β(1)粘附，这是表皮生长中主要角质形成细胞的所有特征。
Wounding of the epidermis signals the transition of keratinocytes from quiescent anchorage on endogenous basement membrane laminin 5 to migration on exposed dermal collagen. In this study, we attempt to characterize activation signals that transform quiescent keratinocytes into migratory leading cells at the wound edge. Previously, we reported that adhesion and spreading on collagen via integrin alpha (2)beta (1) by cultured human foreskin keratinocytes (HFKs) requires RhoGTP, a regulator of actin stress fibers. In contrast, adhesion and spreading on laminin 5 requires integrins alpha (3)beta (1) and alpha (6)beta (4) and is dependent on phosphoinositide 3-hydroxykinase (Nguyen, B. P., Gil, S. G., and Carter, W. G. (2000) J. Biol. Chem. 275,31896-31907). Here, we report that quiescent HFKs do not adhere to collagen but adhere and spread on laminin 5. By using collagen adhesion as one criterion for conversion to a "leading wound cell," we found that activation of collagen adhesion requires elevation of RhoGTP. Adhesion of quiescent HFKs to laminin 5 via integrin alpha (3)beta (1), and alpha (6)beta (4) is sufficient to increase levels of RhoGTP required for adhesion and spreading on collagen. Consistently, adhesion of quiescent HFKs to laminin 5, but not collagen, also promotes expression of the precursor form of laminin 5, a characteristic of leading keratinocytes in the epidermal outgrowth. We suggest that wounding of quiescent epidermis initiates adhesion and spreading of keratinocytes at the wound edge on endogenous basement membrane laminin 5 via alpha (3)beta (1), and alpha (6)beta (4) in a Rho-independent mechanism. Spreading on endogenous laminin 5 via alpha (3)beta (1), is necessary but not sufficient to elevate expression of precursor laminin 5 and RhoGTP, allowing for subsequent collagen adhesion via alpha (2)beta (1), all characteristics of leading keratinocytes in the epidermal outgrowth.